This application addresses broad Challenge Area (06) Enabling Technologies and specific Challenge Topic, 06-HL-109: Generate Reagents for Studying Lung Cell Biology and Disease Progression. The application focuses on the compelling need to generate cell-surface marker specific reagents useful for identification, study, and isolation of pulmonary stem/progenitor cells. The lung contains a large number of diverse cell types that produce and maintain lung structure and function. Our limited understanding of the complex cellular composition, anatomy, and function of this tissue has slowed the establishment of effective tissue regenerative (repair) and/or cell replacement (transplantation) therapies. We propose to generate and characterize a comprehensive panel of highly useful monoclonal antibodies that will target cell-surface markers on subsets of pulmonary stem and progenitor cell populations. Our approach will be to use currently available model systems of lung repair/regeneration as enriched sources of stem and progenitor cells, to use immunization methods that selectively promote immune responses to cells found in regenerating lung and not in normal lung, and to use tissue- and cell-based antibody screening strategies that allow rapid detection of monoclonal antibodies directed against cell surface molecules. This panel of reagents will be of broad use to the scientific community, and will enable studies of normal lung biology, lung regeneration and repair, the identification of candidate markers for clinical diagnosis of pulmonary disease, and may impact the development of cellular therapies for the treatment of various pulmonary diseases. PUBLIC HEALTH RELEVANCE: This application focuses on the compelling need to generate cell-surface marker specific reagents useful for identification, study, and isolation of lung stem/progenitor cells. This panel of reagents will be of broad use to the scientific community, and will enable studies of normal lung biology, lung regeneration and repair, the identification of candidate markers for clinical diagnosis of lung disease, and may impact the development of cellular therapies for the treatment of various lung diseases.